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NDT Advance Access published online on September 23, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl523
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received April 26, 2006
Accepted August 7, 2006

Original Article

Strain susceptibility to active induction and passive transfer of experimental autoimmune glomerulonephritis in the rat

John Reynolds 1 *, Amina Albouainain 1, Mark Anthony Duda 1, David John Evans 1, and Charles Dickson Pusey 1

1 Renal Section, Division of Medicine, Imperial College London, Hammersmith Campus, London W12 ONN, UK

* To whom correspondence should be addressed.
John Reynolds, E-mail: john.reynolds{at}imperial.ac.uk



  Abstract

Background. Previous studies have shown that different inbred rat strains vary in their susceptibility to experimental autoimmune glomerulonephritis (EAG). The Wistar Kyoto (WKY) rat is highly susceptible and develops crescentic glomerulonephritis, while the Lewis (LEW) rat is resistant. When immunized with collagenase-solubilized rat glomerular basement membrane (GBM), both strains produce circulating autoantibodies reactive with rat GBM by enzyme-linked immunosorbent assay, but only the WKY rat shows strong linear deposits of IgG on the GBM.

Methods. We investigated the hypothesis that differences in the characteristics of the anti-GBM antibodies produced, or in the inflammatory response to antibody deposition, could account for susceptibility.

Results. We found that circulating anti-GBM antibodies from WKY rats immunized with GBM were present at a higher concentration than those from LEW rats. Antibodies from WKY rats also recognized the rat {alpha}3 chain of type IV collagen [{alpha}3(IV)NC1], whereas those from LEW rats did not. Antibody eluted from the kidneys of WKY rats with EAG induced by GBM showed a higher affinity for GBM and recombinant rat {alpha}3(IV)NC1 than circulating antibody. This eluted antibody bound strongly to normal kidney sections from both WKY and LEW rats. Passive transfer of eluted anti-GBM antibodies from WKY rats with EAG resulted in similar binding of IgG to the GBM of WKY and LEW rats at 24 h. However, only the WKY recipients went on to develop crescentic glomerulonephritis by 28 days.

Conclusions. This study demonstrates that the characteristics of the anti-GBM antibodies induced in WKY rats contribute to their susceptibility to EAG. However, the passive transfer experiments reveal that factors related to the inflammatory response to antibody deposition are also important in determining susceptibility. A combination of these genetic influences could explain the variation in severity of human anti-GBM disease.

Keywords: anti-GBM antibodies; experimental autoimmune glomerulonephritis (EAG); genetic susceptibility; glomerular basement membrane (GBM); Lewis (LEW) rat; Wistar Kyoto (WKY) rat.
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